Homocysteine Predicts Incident Isolated Systolic Hypertension in Older Adults
Untreated isolated systolic hypertension (ISH) indicates arterial stiffening and carries a risk for both stroke and cardiovascular disease. Elevated plasma homocysteine, a metabolite of the essential amino acid methionine, has been linked to vascular stiffness. 187 normotensive (defined as systolic blood pressure (SBP) < 160 mmHg and diastolic blood pressure < 90 mmHg) men and women (mean age 71.29 + 6.3 yrs) were followed for an average of 7 years for incident ISH. ISH was defined as a SBP ≥160 mmHg (while maintaining a DBP of < 90 mmHg) at least one time at 3 year follow-up visits, or the initiation of antihypertensive therapy. The mean baseline systolic and diastolic blood pressures (DBP) were 127 and 69 mmHg, respectively. Over the 7 year period, 59(31.5%) participants developed ISH, 76% qualified by antihypertensive use, and 24% by blood pressure values. The Kaplan Meier Estimate of 7 year survival free from ISH was 67% (95% CI: 61%, 74%). The relationship between incident ISH and the traditional cardiovascular risk factors, creatinine, homocysteine, and carotid artery intima-media wall thickness (IMT) was assessed by Cox proportional hazards regression. The strongest predictor of incident ISH was baseline SBP. For participants with baseline SBPs of < 130, 130-139, and 140+ mmHg, the corresponding 7 year survival free from ISH was 80% (95% CI: 73%, 88% ), 53% (95%CI: 38%, 67%), and 44% (95% CI: 26%, 62%). Factors independently associated with time to ISH were higher triglycerides (upper tertile,RR=2.0, p=0.012), homocysteine levels (> 12.0 μmol/l, RR=2.2, p=0.005), and baseline SBP (per 10 mmHg,RR=1.4, p=0.003). The results were similar when the analysis was restricted to the 157 participants with a baseline SBP of < 140 mmHg. Baseline IMT was found to be univariately related to time to ISH (RR per each 1.0 mm increment=3.0; p=0.016). In multivariate analysis, this association remained independent of triglycerides and homocysteine, but not baseline SBP (RR per each 1.0 mm increment=2.5; p=0.049). In conclusion, among normotensive older adults, 32% can be expected to develop ISH over a 7 year period, and higher triglyceride and homocysteine levels are risk factors.